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Abstract
Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαβR-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77–88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).
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1 State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, People’s Republic of China; Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China
2 Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, People’s Republic of China
3 The Center for Infection & Immunity Study, School of Medicine, Shenzhen campus of Sun Yat-sen University, Shenzhen, People’s Republic of China
4 Infectious diseases department, First Affiliated Hospital, Xinjiang Medical University, Urumqi, People’s Republic of China
5 Kashi Center for Disease Control and Prevention, Kashi, People’s Republic of China
6 Yushu Prefecture Center for Disease Control and Prevention, Yushu, People’s Republic of China
7 State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
8 Kashi first people’s hospital, Kashi, People’s Republic of China
9 State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China
10 Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, People’s Republic of China
11 State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, People’s Republic of China; Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; Institute of Public Health, Nankai University, Tianjin, People’s Republic of China